Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy, Charité-Universitätsmedizin Berlin, 14050 Berlin, Germany.
Br J Clin Pharmacol. 2013 Mar;75(3):822-30. doi: 10.1111/j.1365-2125.2012.04388.x.
Angiotensin-II receptor 1 antagonists (AT₁-antagonists) may cause severe and even lethal fetopathy in late pregnancy. However, exposure still occurs in spite of warnings in package leaflets. This study aimed to assess the risk of fetopathy, the sensitive time window, and possible new symptoms in prospective as well as retrospective cases with AT₁-antagonist treatment during the second or third trimester of pregnancy.
Patients were enrolled by the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy between 1999 and 2011 through risk consultation. Symptoms defined as indicative of AT₁-antagonist fetopathy were: oligo-/anhydramnios, renal insufficiency, lung hypoplasia, joint contractures, skull hypoplasia and fetal/neonatal death.
In 5/29 (17%) prospectively enrolled cases with AT₁-antagonist exposure beyond the first trimester oligo-/anhydramnios was diagnosed. Two infants showed additional symptoms of fetopathy. The risk is more than 30% if treatment continues beyond the 20th week of pregnancy. Oligo-/anhydramnios was reversible after AT₁-antagonist withdrawal. Among 16 retrospective case reports, three infants presented with a thrombosis of the inferior vena cava in the vicinity of the renal veins. Four out of 13 live births did not survive.
Our survey suggests that the risk increases with duration of AT₁-antagonist treatment into late pregnancy and oligo-/anhydramnios may be reversible after AT₁-antagonist discontinuation. Thrombosis of inferior vena cava may be a new feature of AT₁-antagonist fetopathy. AT₁-antagonist medication during pregnancy constitutes a considerable risk and must be discontinued immediately. In case of indicative diagnostic findings in either the fetus or newborn, previous maternal AT₁-antagonist exposure should be considered.
血管紧张素 II 受体 1 拮抗剂（AT₁-拮抗剂）在妊娠晚期可能导致严重甚至致命的胎儿病变。然而，尽管包装说明书中有警告，但仍有暴露发生。本研究旨在评估在妊娠第二或第三孕期使用 AT₁-拮抗剂治疗的前瞻性和回顾性病例中胎儿病变的风险、敏感时间窗口以及可能的新症状。
1999 年至 2011 年，柏林临床致畸与妊娠期间药物风险评估研究所通过风险咨询招募了患者。将以下症状定义为 AT₁-拮抗剂胎儿病变的指征：羊水过少/无羊水、肾功能不全、肺发育不全、关节挛缩、颅骨发育不全和胎儿/新生儿死亡。
在 5/29（17%）例前瞻性纳入的病例中，在妊娠第一 trimester 后发现羊水过少/无羊水。两名婴儿出现了额外的胎儿病变症状。如果治疗持续到妊娠 20 周后，风险超过 30%。AT₁-拮抗剂停药后，羊水过少/无羊水可逆转。在 16 例回顾性病例报告中，有 3 例婴儿在下腔静脉附近的肾静脉中出现血栓形成。13 例活产儿中有 4 例未存活。
我们的调查表明，随着 AT₁-拮抗剂治疗进入晚期妊娠的持续时间增加，风险增加，并且 AT₁-拮抗剂停药后羊水过少/无羊水可能是可逆的。下腔静脉血栓形成可能是 AT₁-拮抗剂胎儿病变的一个新特征。妊娠期间使用 AT₁-拮抗剂构成相当大的风险，必须立即停药。如果在胎儿或新生儿中出现提示性诊断结果，应考虑之前母亲的 AT₁-拮抗剂暴露。
